E-CELL Project Overview:
Towards Integrative Simulation of Cellular Processes
Masaru Tomita

12

mt@sfc.keio.ac.jp
Yuri Matsuzaki

13

yuri@sfc.keio.ac.jp

Kenta Hashimoto

13

kem@sfc.keio.ac.jp
Ryo Matsushima

13

ryo@sfc.keio.ac.jp

12
Katsuyuki Yugi

12
Fumihiko Miyoshi

t95980ky@sfc.keio.ac.jpt95894fm@sfc.keio.ac.jp

12
Sakura Tanida

3
45

13

shafi@sfc.keio.ac.jp
Kanako Saito

13

t95401ks@sfc.keio.ac.jp
Hisako Nakano

14s96649hn@sfc.keio.ac.jp

Thomas S. Shimizu

t94613st@sfc.keio.ac.jp
12Kouichi Takahashi

15

tss26@cus.cam.ac.uk

Laboratory for Bioinformatics
Department of Environmental Information
School of Media and Governance
Department of Policy Management
Keio University, 5322 Endo, Fujisawa, 252-8520 Japan
Department of Zoology, Cambridge University, CB2 3EJ, UK

1 Introduction
The E-CELL project [?] was launched in 1996 at Keio University in order to model and simulate
various cellular processes with the ultimate goal of simulating the cell as a whole. The rst version ofthe E-CELL simulation system, which is a generic software package for cell modeling, was completedin 1997. The E-CELL system enables us to model not only metabolic pathways but also other higherorder cellular processes such as protein synthesis and membrane transport within the same framework.
These various processes can then be integrated into a single simulation model.
Using the E-CELL system, we have successfully constructed a virtual cell with 127 genes sucientfor \self-support". The gene set was selected from the genome of Mycoplasma genitalium, the organism
having the smallest known genome. The set includes genes for transcription, translation, the glycolysis
pathway for energy production, membrane transport, and the phospholipid biosynthesis pathway formembrane structure.

2 Ongoing Research
We are now in the second phase of the project, in which the following cellular processes are being
modeled using the E-CELL system: Other metabolic pathways, including the TCA cycle, the pentose-phosphate cycle, and biosyn-

thesis pathways for nucleotides and amino acids (Fig. 1).

 DNA replication and procaryotic cell cycle [?].
 Lambda phage gene regulatory network.
 Signal transduction for bacterial chemotaxis [?].
 Kinetic model of human red blood cell [?].

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Figure 1:\Self-Supporting" Cell Model '98.

3 Concluding Remarks
Besides cell modeling work described above, the E-CELL simulation software itself is being improvedin several important ways [?]. For example, reaction rules and substance de nitions for simulation
can now be written as a spread sheet table using any commercially or publicly available spread sheet
software. Methodologies for time series analyses of metabolic network using the E-CELL system arealso being developed [?]. The E-CELL system will be made available in early 1999 from our website.

Acknowledgements
We would like to thank Craig Venter and Clyde Hutchison for their support in an early stage of theE-CELL project. Doug Brutlag, Peter Karp and Nobuyoshi Shimizu also gave us useful comments atthe beginning of the project. The E-CELL project is funded in part by a Grant-in-Aid for Scienti c
Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan.

References[1] Tomita, M., Hashimoto, K., Takahashi, K., Shimizu, T., Matsuzaki, Y., Miyoshi, F., Saito, K.,Tanida, S., Yugi, K., Venter, J.C., and Hutchison, C., E-CELL: Software environment for wholecell simulation, Bioinformatics (to appear).
[2] Hashimoto, K. et al., Modeling of transcription, translation and DNA replication using the ECELL simulation system, Genome Informatics 1998, Universal Academy Press, 1998.
[3] Matsuzaki, Y. et al., Modeling of the signal transduction for bacterial chemotaxis using theE-CELL simulation system, Genome Informatics 1998, Universal Academy Press, 1998.
[4] Matsushima, R. et al., Modeling of human red blood cell using the E-CELL simulation system,
Genome Informatics 1998, Universal Academy Press, 1998.
[5] Takahashi, K. et al., Modeling theory and software architecture of the E-CELL simulation system,
Genome Informatics 1998, Universal Academy Press, 1998.
[6] Saito, H. et al., Multivariate time series analysis of metabolic network using the E-CELL simulation system, Genome Informatics 1998, Universal Academy Press, 1998.
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